Single-cell transcriptomic analysis reveals seed cells and microenvironmental crosstalk in gastric cancer peritoneal metastasis
Abstract
Peritoneal metastasis is the most frequent and lethal metastatic pattern in gastric cancer, yet the identity of metastatic seed cells and the accompanying microenvironmental remodeling remain poorly defined. Integrated single-cell RNA sequencing analysis of cells derived from primary gastric tumors and peritoneal metastases revealed markedly distinct cellular compositions. Copy number variation and clonality analyses indicated that peritoneal metastases originate from primary tumor subclones with chromosome 12 amplification. Trajectory analysis identified epithelial cell cluster 2 as a transitional population exhibiting bifurcating cell fates, marked cellular plasticity, and metabolic adaptability. These cells were defined as peritoneal metastasis–associated epithelial cells (PMAECs) and proposed as a putative metastatic seed-cell population. Integrated machine learning identified five PMAEC marker genes, and a nomogram for predicting peritoneal dissemination risk was constructed and validated in an independent cohort, demonstrating robust predictive and prognostic performance. Single-cell dissection of the tumor microenvironment revealed extensive remodeling of macrophage, fibroblast, T cell, and B cell subpopulations, along with aberrantly activated signaling networks between PMAECs and multiple microenvironmental components in peritoneal metastases. This study provides a comprehensive single-cell atlas of gastric cancer peritoneal metastasis and delineates the coordinated evolution of metastatic seed cells and microenvironmental crosstalk, thereby offering potential biomarkers and therapeutic targets.
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BibTeX
@article{chen2026singlecell,
title = {{Single-cell transcriptomic analysis reveals seed cells and microenvironmental crosstalk in gastric cancer peritoneal metastasis}},
author = {Weiyi Chen and Ewetse Paul Maswikiti and Yifan Li and Huanhuan Ma and Kai Wang and Dan Zou and Ying Yan and Jingwei Ma and Yali Li and Yile Qi and Jing Liu and Lingzhi Liao and Jiahui Ma and Hao Chen},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-74547-8},
url = {https://www.nature.com/articles/s41598-026-74547-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell transcriptomic analysis reveals seed cells and microenvironmental crosstalk in gastric cancer peritoneal metastasis
AU - Weiyi Chen
AU - Ewetse Paul Maswikiti
AU - Yifan Li
AU - Huanhuan Ma
AU - Kai Wang
AU - Dan Zou
AU - Ying Yan
AU - Jingwei Ma
AU - Yali Li
AU - Yile Qi
AU - Jing Liu
AU - Lingzhi Liao
AU - Jiahui Ma
AU - Hao Chen
PY - 2026
DA - 2026/10/05
JO - Scientific Reports
DO - 10.1038/s41598-026-74547-8
UR - https://www.nature.com/articles/s41598-026-74547-8
AB - Peritoneal metastasis is the most frequent and lethal metastatic pattern in gastric cancer, yet the identity of metastatic seed cells and the accompanying microenvironmental remodeling remain poorly defined. Integrated single-cell RNA sequencing analysis of cells derived from primary gastric tumors and peritoneal metastases revealed markedly distinct cellular compositions. Copy number variation and clonality analyses indicated that peritoneal metastases originate from primary tumor subclones with chromosome 12 amplification. Trajectory analysis identified epithelial cell cluster 2 as a transitional population exhibiting bifurcating cell fates, marked cellular plasticity, and metabolic adaptability. These cells were defined as peritoneal metastasis–associated epithelial cells (PMAECs) and proposed as a putative metastatic seed-cell population. Integrated machine learning identified five PMAEC marker genes, and a nomogram for predicting peritoneal dissemination risk was constructed and validated in an independent cohort, demonstrating robust predictive and prognostic performance. Single-cell dissection of the tumor microenvironment revealed extensive remodeling of macrophage, fibroblast, T cell, and B cell subpopulations, along with aberrantly activated signaling networks between PMAECs and multiple microenvironmental components in peritoneal metastases. This study provides a comprehensive single-cell atlas of gastric cancer peritoneal metastasis and delineates the coordinated evolution of metastatic seed cells and microenvironmental crosstalk, thereby offering potential biomarkers and therapeutic targets.
SN - 2045-2322
ER -